Update Management of cow’s milk protein allergy in infants
Cow’s milk is a leading cause of food allergy especially in infants and children. ‘Diagnosis and Rationale for Action against Cow’s Milk Allergy’ published by the World Allergy Organization has underlined that there is not enough information concerning geographical trends in cow’s milk allergy (CMA) in children or adults. CMA is a global challenge and collaboration of the national and international scientific communities is essential to produce and update practical guidelines for CMA.
Symptoms of cow’s milk allergy are non-specific; as a result, suspected cow’s milk allergy is far more common than proven allergy to cow’s milk. Cow’s milk allergy in infants is therefore most probably a fairly uncommon clinical picture; cow’s milk allergy is estimated to occur in less than one per cent of infants. The only valuable additional diagnostic tool is food challenge, preferably double blind. Therapy consists of a formula free of cow’s milk (preferably containing extensively hydrolysed whey protein) from the moment the mother ceases nursing her child until the age of 6-12 months. Solids can be introduced in the usual fashion; there is no scientific basis for introducing them in a step by step fashion. Prevention of cow’s milk allergy by using hypoallergenic formula (partially hydrolysed cow milk protein) in the first year of life has been shown to be unsuccessful, and can no longer be recommended. In the future, oral immunotherapy may be a promising new treatment for cow’s milk allergy.
Between 5% and 15% of infants show symptoms suggesting adverse reactions to cow’s milk protein (CMP),1 while estimates of the prevalence of cow’s milk protein allergy (CMPA) vary from 2% to 7.5%.2 Differences in diagnostic criteria and study design contribute to the wide range of prevalence estimates and underline the importance of an accurate diagnosis, which will reduce the number of infants on inappropriate elimination diets. CMPA is easily missed in primary care settings and needs to be considered as a cause of infant distress and diverse clinical symptoms. Accurate diagnosis and management will reassure parents. CMPA can develop in exclusively and partially breast-fed infants, and when CMP is introduced into the feeding regimen. Early diagnosis and adequate treatment decrease the risk of impaired growth
There are guidelines for the use of dietary products for the prevention and treatment of CMPA. However, there are currently no guidelines that specifically assist primary care physicians and general paediatricians in the accurate diagnosis and management of CMPA. This document aims to meet this need. However, these recommendations may need adaptation to reflect local situations and, because they are not evidence based, need to be prospectively validated and revised in the future. Despite these caveats, the authors believe application of these recommendations will improve the diagnostic and therapeutic skills of physicians in primary care.
Cow’s milk protein (CMP) is usually one of the first complementary foods to be introduced into the infant’s diet and is commonly consumed throughout childhood as part of a balanced diet. CMP is capable of inducing a multitude of adverse reactions in children, which may involve organs like the skin, gastrointestinal (GI) tract or respiratory system. The diagnosis of CMP-induced adverse reactions requires an understanding of their classification and immunological basis as well as the strengths and limitations of diagnostic modalities. In addition to the well-recognised, immediate-onset IgE-mediated allergies, there is increasing evidence to support the role of CMP-induced allergy in a spectrum of delayed-onset disorders ranging from GI symptoms to chronic eczema. The mainstay of treatment is avoidance of CMP; this requires dietetic input to ensure that this does not lead to any nutritional compromise.
EVALUATION OF AN INFANT WITH SUSPECTED CMPA
A comprehensive history (including a family history of atopy) and careful physical examination form the foundation of both algorithms. The risk of atopy increases if a parent or sibling has atopic disease (20–40% and 25–35%, respectively), and is higher still if both parents are atopic (40–60%). In comparison to cow’s milk formula-fed infants, exclusive breast feeding during the first 4–6 months of life reduces the risk for CMPA and most severe allergic manifestations during early infancy. The distinction between breast-fed and formula-fed infants reflects the importance of ensuring an adequate duration of breast feeding. Management principles also differ. The management of breast-fed infants depends on reducing the maternal allergen load and strict avoidance of CMP in supplementary feeding. It is recommended that exclusive or partial breast feeding is continued, unless alarm symptoms require a different management.The earlier CMPA develops, the greater the risk of growth retardation
Clinical manifestations of CMA
|Gastrointestinal tract||Frequent regurgitation|
|Constipation (with/without perianal rash)|
|Blood in stool|
|Iron deficiency anaemia|
|Swelling of lips or eye lids (angio-oedema)|
|Urticaria unrelated to acute infections, drug intake or other causes|
|Respiratory tract||Runny nose (otitis media)20 21|
|(unrelated to infection)||Chronic cough|
|General||Persistent distress or colic (wailing/irritable for ⩾3 h per day) at least 3 days/week over a period of >3 weeks|
*Infants with CMPA in general show one or more of the listed symptoms.
Alarm symptoms and findings indicating severe CMPA as the possible cause
|Organ involvement||Symptoms and findings|
|Gastrointestinal tract||Failure to thrive due to chronic diarrhoea and/or refusal to feed and/or vomiting|
|Iron deficiency anaemia due to occult or macroscopic blood loss|
|Endoscopic/histologically confirmed enteropathy or severe colitis|
|Skin||Exudative or severe atopic dermatitis with hypoalbuminaemia or failure to thrive or iron deficiency anaemia|
|Respiratory tract||Acute laryngoedema or bronchial|
|(unrelated to infection)||obstruction with difficulty breathing|
ALGORITHM FOR THE DIAGNOSIS AND MANAGEMENT OF CMPA IN FORMULA-FED INFANTS
Patients with life-threatening, particularly respiratory symptoms or anaphylaxis, conditions need to be referred immediately to an emergency department experienced in the treatment of this condition. In all the other situations, the initial step in the diagnostic work-up for CMPA is clinical assessment accompanied by history taking, including establishing whether there is a family history of atopic disease .
The algorithm differs according to the severity of symptoms. If the infant does not present alarm symptoms , the case is considered as mild-to-moderate suspected CMPA, and a diagnostic elimination diet should be initiated. Infants presenting with symptoms such as angio-oedema of lips and/or eyes, urticaria and immediate vomiting are likely to have IgE-mediated allergy. In the case of IgE-mediated allergy, improvement (and normalisation) offers a safety net before challenge. A positive SPT increases the likelihood of a positive food challenge but not the severity of the reaction. In the study from Celik-Bilgili and coworkers, 60% of the patients with a RAST class 1, 50% in class 2, 30% in class 3 and even 20% in class 4 had a negative food challenge
DIAGNOSTIC WORK-UP IN SYMPTOMATIC INFANTS WITH NO ALARM SYMPTOMS (MILD-TO-MODERATE MANIFESTATIONS)
In a case of suspected mild-to-moderate CMPA, CMP elimination should start with a therapeutic formula for CMPA. The guidelines define a therapeutic formula as one that is tolerated by at least 90% (with 95% confidence) of CMPA infants.31 These criteria are met by some eHFs based on whey, casein or another protein source, and by amino acid-based formulae (AAF). Preferentially, all supplementary food should be stopped during the diagnostic elimination diet. If this is not possible in infants beyond 6 months, only a few supplementary foods should be allowed with dietary counselling. Nevertheless, the diet should not contain CMP or hen’s eggs, soy protein or peanut. Referral to a paediatric specialist and dietary counselling may be needed for patients who do not improve. In such cases, further elimination of other allergenic proteins such as fish and wheat may be appropriate. In most cases, the therapeutic elimination diet should be given for at least 2 weeks, although this may need to be increased to up to 4 weeks in gastrointestinal manifestations and atopic dermatitis before deciding that the intervention has failed.
eHFs that meet the definition of a therapeutic formula are the first choice. An AAF is indicated: if the child refuses to drink the eHF, but accepts the AAF (eHF has a more bitter taste than AAF), if the symptoms do not improve on the eHF after 2–4 weeks, or if the cost–benefit ratio favours the AAF over the eHF. The cost–benefit ratio of AAF versus eHF is difficult to elaborate in this global overview since health care cost differs substantially from country to country, as does the cost of the eHF and the AAF, which in some countries is (partially) reimbursed by national or private health insurance. The risk of failure of eHF is up to 10% of children with CMPA.4 In the latter case, clinicians should refer to a specialist for further diagnostic work-up.
Children may react to residual allergens in eHF, which may be one reason for the failure. The residual allergens in eHFs seem to be more likely to produce gastrointestinal and other non-IgE-associated manifestations compared to AAFs.4 6 32 However, IgE-related reactions have also been reported with eHF. In such cases, clinicians should consider an AAF which has been proven to be safe and nutritionally adequate to promote weight gain and growth. In some situations, the infant may be initially switched to an AAF, especially if they experience multiple food allergies, specific gastrointestinal manifestations or both. In these instances, the potential benefits of an AAF may outweigh its higher cost. If symptoms do not disappear on the AAF, another diagnosis should be considered.
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Links Article Cow’s Milk Allergy
- The Natural History of Cow’s Milk Allergy
- Clinical Manifestation of Cow’s Milk Protein Allergy as a Complex Disorders
- Update Management of cow’s milk protein allergy in infants
- Special Reference Cow Milk Allergy
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